Amyloid β peptides mediate hypoxic augmentation of Ca2+ channels

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Abstract
Clinical studies indicate that neurodegeneration caused by Alzheimer's amyloid β peptide (AβP) formation can be triggered or induced by prolonged (chronic) hypoxia. Here, we demonstrate that 24-h culture of PC12 cells in 10% O2 leads to induction of a Cd2+-resistant Ca2+ influx pathway and selective potentiation of l-type Ca2+ current. Both effects were suppressed or prevented by a monoclonal antibody raised against the N′-terminus of AβP, and were fully mimicked by AβP1−40 and AβP1−42, but not by AβP40−1. Potentiation of l-type currents was also induced by exposure to AβP25−35. Our results indicate that hypoxia induces enhancement of Ca2+ channels, which is mediated by increased AβP formation.